Figure 2.

GalNAc AON-Induced Nephrotoxicity Is Recapitulated using Naked AONs In Vitro

(A and B) Histological evaluation of rat kidneys showing histopathological manifestations induced by GalNAc and naked AON-B (20 and 40 mg/kg, respectively) (A) and by GalNAc AON-D and GalNAc AON-E (50 mg/kg dose) (B). Wide, open arrows indicate examples of areas with tubular degeneration and/or regeneration. Fine, filled arrows indicate necrotic or apoptotic cells. 1/4 means that one animal in the group (n = 4) showed minimal tubular degeneration. 4/4 means that all animals in the group (n = 4) showed minimal to moderate lesions. H&E, 20× magnification. Lower panels are enlarged images of sections shown in upper panels, except for vehicle in (B), which is from a different section. (C and D) The toxicity potential of GalNAc AON-D and -E is revealed in PTECs when AONs are applied in their naked form only, as manifested by elevated EGF at day 6 (C) and by morphological abnormalities visible under the bright field (20×, representative of n = 3) at day 9, as shown for the 100-μM concentration (D). Data in (C) represent means and SD (n = 3).